The matrix proteins of bones and teeth play key roles in the structure and function of these tissues. Our objective is to study the structure and function of these macromolecules and to understand the regulation of their expression. The primary structures of bone and tooth matrix proteins have been studied by constructing recombinant cDNA libraries from bone or ameloblast cell mRNA. cDNAs encoding several bone and tooth matrix proteins were isolated. The clones and antibodies were used to determine the primary structure and mode of expression of the genes in cultured cells and intact tissue. These studies showed the matrix proteins had distinct spatial and temporal patterns of expression during bone cell differentiation both in vitro and in vivo. Using the cDNAs as probes we have isolated genomic DNA and analyzed the control of certain of these genes at the nuclear level. The human biglycan promoter was shown to contain a functional G rich region between -262 and -218 that bound to a novel 25 kDa nuclear factor present in cultured bone cells. The controlling elements of the BSP gene were also characterized and indicated that the basal promoter was regulated by a transcription factor known as YY1 (yin yang 1). Studies are underway using transgenic mice to identify the function of the matrix proteins and the elements that regulate their expression during development and aging in vivo.